Immunization registries are confidential, computerized information systems that collect and consolidate vaccination data from multiple health-care providers, generate reminder and recall notifications, and assess vaccination coverage within a defined geographic area. A registry with added capabilities, such as vaccine management, adverse event reporting, lifespan vaccination histories, and linkages with electronic data sources, is called an immunization information system (IIS). This report summarizes data from CDC's 2005 Immunization Information System Annual Report (IISAR), a survey of grantees in 50 states, five cities, and the District of Columbia (DC) that receive funding under section 317b of the Public Health Service Act. These data indicated that approximately 56% of U.S. children aged <6 years participated in an IIS, an increase from 48% in 2004. Moreover, 75% percent of public vaccination provider sites and 44% of private vaccination provider sites submitted vaccination data to an IIS during July-December 2005. These findings underscore the need to increase the number of participating children, from the current 13 million to approximately 21 million, to assure 95% participation of children aged <6 years and improve the effectiveness of U.S. immunization programs.